Radiochemistry

The lack of radiochemical methods to introduce radioactive labels into small molecules and large macromolecules alike limits the pharmacological space that is accessible with nuclear imaging. We develop new chemical platform techniques that give access to an unprecedented radiochemical space and allow flexible radiotracer design and manufacture in clinical routines.

Sulfonium salt chemistry for aromatic labelling with fluorine-18

Sulfonium salts allow direct labelling of small drug-like molecules with fluorine-18. The appeal of this approach is the ability to label a broad range of bioactive molecules under conditions that mirror conventional substitution reactions with fluoride-18. 

To overcome the synthetic limitations associated with sulfonium salt formation, we developed a novel intramolecular ring-closing reaction that gives access to highly functionalized dibenzothiophene sulfonium salts. The strategy provides a flexible platform and facilitates the development of novel radiotracers for imaging with positron emission tomography.

Iodine click chemistry for multimodality imaging probes

The ability to study biological processes across cellular and macroscopic scales remains a fundamental goal for molecular imaging. However, no imaging modality meets the need for high resolution, high sensitivity, and deep tissue penetration. With the aim to address this need, we developed a new approach to multiscale multimodal imaging based on a one‐pot synthesis of dual optical and nuclear labelling reagents and applied it to the dual labelling of an antibody.

Translational Imaging

Imaging of multiple drug resistance

Multiple drug resistance (MDR) is a major clinical challenge for the successful treatment of many prevalent diseases of the central nervous system as well as cancers. In order to evaluate the role of the efflux transporters in the development of MDR and moreover, to provide diagnostic tools to quantify efflux pump activity in vivo, prodrug tracers for dynamic imaging with PET have been developed.

Clinical studies

We provide bespoke imaging agents for clinical research carried out at UCL, UCL Hospitals and partner institutions, and radiotracers developed in-house at the CRC into first in human studies.

Image-Derived Enzymatic Adrenal Lateralisation (IDEAL)

Hypertension is a leading cause of premature morbidity and death globally. Although lifestyle changes and medication can be effective, elevated blood pressure due to secondary disease is difficult to control. This is particularly the case for primary hyperaldosteronism (PHA), which is characterized by excessive aldosterone production by the adrenal gland/s. PHA occurs in 5–10% of patients with hypertension and in 15–25% of those with treatment-resistant hypertension. Although PHA is recognized to be the most common, potentially curable cause of secondary hypertension, only a few patients receive appropriate treatment and care as there are no practical methods to identify those who are likely to benefit from curative surgery.

We have developed AldoView, a new radiotracer labelled with fluorine-18, for imaging with positron emission tomography (PET). In preclinical studies in mice, AldoView showed a favourable pharmacokinetic profile. The tracer was found to demarcate areas with high aldosterone synthase expression levels in human adrenal tissue with high specificity.

With the aim to evaluate the potential of AldoView for non-invasive, image-derived enzymatic lateralization of aldosterone production by the adrenal gland/s with PET, first in human imaging studies will commence in the close future.